Same Gene Mutations Tied to 12 Cancers; Research Finding May Lead to Better Treatment

Same Gene Mutations Tied to 12 Cancers

Research Finding May Lead to Better Treatment

RON WINSLOW

Washington University’s Li Ding and others found that 12 types of cancer share the same genetic mutations.Robert J. Boston/Washington University School of Medicine

Oct. 16, 2013 6:46 p.m. ET

New results from the Cancer Genome Atlas research project identify a host of genetic mutations that are common among 12 different types of cancer, reflecting the growing understanding that tumors can be defined by their underlying biology rather than their location in the body. The report, published Wednesday by the journal Nature, is part of an effort to compile a list of all genetic mutations that can trigger the development and progression of tumors. Experts hope such a list will guide diagnosis of cancer and spur development of drugs that target the genetic anomalies, a strategy known as precision medicine.The approach already is changing the treatment of some patients with melanoma, lung cancer and some other malignancies—sometimes with impressive results. But researchers say that to enable more patients to benefit, much more information is needed about specific mutations that fuel cancer’s growth.

The Cancer Genome Atlas, funded by the National Institutes of Health, already has yielded a trove of findings that show a specific cancer, such as breast cancer, can be caused by different mutations. By contrast, the new study identifies mutations that are common across cancers.

Researchers analyzed genes from 3,281 tumors culled from cancers of the breast, uterus, lung, colon, brain, kidney and other sites. The goal, said Li Ding, a researcher at the Genome Institute at Washington University in St. Louis and senior author of the study, “is to come up with a common reference gene panel that could be used for diagnosing and designing treatment strategies for patients.”

Researchers estimate that essentially all cancers are fueled by between 200 and 400 mutations, many of which are in genes that regulate molecular pathways responsible for cell growth. The mutations can cause normal cellular process to go awry, causing cancer.

Dr. Ding said that with the new study, combined with plans by an international consortium to study even more cancers, “I’m confident we are getting close to a complete list of cancer genes.”

She and her colleagues identified 127 genes that had a high likelihood of being drivers of the disease, she said.

William Pao, director of personalized cancer medicine at Vanderbilt University School of Medicine, said many of the variants identified in the study are already known, but the role of others is just emerging.

Dr. Pao described the report as a “blueprint” that provides a “foundation for discovering new therapies and effective ways of treating cancer.”

One of the mutations identified in the study, in a gene called BRAF, highlights both the promise and the challenge of finding what role the same mutation may play in different types of tumors.

The BRAF mutation already is implicated in more than half of cases of melanoma; in the new study, it was found in 7% of certain lung cancer tumors, 4% of colon cancer malignancies and in smaller fractions of brain, bladder, head-and-neck, kidney and ovarian cancers.

Roche Holding AG’s drug Zelboraf is approved for melanoma patients with a BRAF mutation, and in small studies it has shown promise among lung-cancer patients with the same mutation. But researchers say other studies indicated the drug used alone has little effect on BRAF-driven colon-cancer tumors.

Health insurers have been reluctant to cover use of a targeted drug in tumors for which it isn’t approved.

Still, said Michael Berger, a genetics researcher at Memorial Sloan-Kettering Cancer Center in New York, the new study suggests “we should be looking for BRAF mutations not just in melanoma but in every other kind of cancer where it might occur in low frequencies” in searching for treatment options.

Deadly Cancers Driven by Relatively Few Mutations, Study Finds

Most common tumors are driven by just two to six DNA mutations, according to a genetic analysis of 3000 tumor samples that brings scientists closer to devising a comprehensive list of all the key mutations that cause cancer or contribute to its progression.

In the study, researchers from Washington University in St. Louis analyzed 3,281 tumors from 12 cancer types, including breast cancer, lung cancer and colon cancer. They found 127 mutated genes in those tumors that appeared to be involved in either in cancer initiation or progression. The results indicate that a relatively small number of genetic changes fuel tumor growth, said Li Ding, senior author on the study.

“This is a really small number. This suggests that only a few driver mutations are required for developing tumors,” said Ding, assistant director of the genome institute at the university, in a phone interview. In the long run, cataloging cancer’s genetic changes “will help develop personalized treatment strategies for each patient.”

The new work, published in the journal Nature, is part of the Cancer Genome Atlas project, a U.S. National Institutes of Health-funded effort to discover what changes make a normal cell cancerous and pinpoint more effective treatments. After performing several studies examining mutated genes found in specific tumor types, researchers in the project are now scanning multiple cancer types simultaneously to find patterns of genetic abnormalities common to different tumors. The ultimate goal is to treat patients with therapies tailored to the specific mutations involved in each individual’s cancer.

Moving Closer

The new study moves researchers closer towards devising a comprehensive list of the key genes involved in cancer, said Ding in a phone interview. Her study, though, is not the final word on this subject, because it only looked at certain types of common mutations and didn’t examine other genetic changes where large chunks of DNA are rearranged abnormally.

Still, given the rapid rate at which researchers are generating cancer genome data, “we have a reasonable chance of identifying most of the core cancer genes” in the next three to five years, Ding said.

One promising result of Ding’s study is that it identified several mutated genes that are bad prognostic factors across a number of cancers, said Thomas Hudson, a genome scientist at the Ontario Institute for Cancer Research, in a phone interview. If confirmed, the findings could help doctors develop new prognostic tests that indicate which patients need the most aggressive treatment, he said.

“Having markers of bad prognosis is really critical” as it may help doctors decide which patients may benefit from drug treatment after surgery to prevent cancer from recurring, said Hudson.

To contact the reporter on this story: Robert Langreth in New York at rlangreth@bloomberg.net